3D Liver Mimics

The liver is one of the important organs in our bodies, playing a vital role in glucose homeostasis, the synthesis of bile acids for the metabolism of cholesterol, and the secretion of proteins to aid clotting. The liver is also primarily responsible environmental toxins, alcohol, cigarette smoke, and for the detoxification of foreign substances (xenobiotics), including drugs. The deterioration in any of its functions can lead to serious health conditions. Hepatocytes are the principal cells in the liver, comprising over 80% of its mass and performing several characteristic functions of this organ. The remaining 30% of the cells are comprised of LSECs, Kupffer cells, and hepatic stellate cells.

Since the liver performs a wide range of complex physiological functions, the definition of a liver mimic has been widely debated. Liver sinusoids in vivo contain layers of hepatocytes and LSECs separated by the Space of Disse, a region comprised primarily of collagen fibers. Oxygen-rich blood from the hepatic artery and the nutrient-rich blood from the portal vein pass through the sinusoids, making them critical to liver function. Furthermore, heterotypic cell-cell interactions between hepatocytes, LSECs and other hepatic cell types occur at the sinusoids. Hence, this region could serve as a reliable hepatic model.

Padma Rajagopalan's group has designed an in vitro hepatic model based on the principle that a biocompatible polyelectrolyte multilayer might serve to mimic the Space of Disse. These model hepatic constructs are comprised of primary rat hepatocytes, an intermediate chitosan-hyaluronic acid polyelectrolyte multilayer (PEM) scaffold, and either primary human Liver Sinusoidal Endothelial Cells (LSECs) or primary rat LSECs. These 3D liver models maintain the phenotype of both cell types simultaneously for up to 4 weeks. The activities of important drug metabolizing Cytochrome P450 enzymes CYP 1A1/2 and CYP3A are three–six fold higher in 3D liver mimics than in other liver models.

Several research projects in CTE are centered around this 3D liver model.